Recently various percutaneous preparations in the form of a preparation to be applied to the skin (for example, plaster, tape, etc.), whereby a drug is administered to the living body via the skin surface, have been developed.
As an example of an estrogen preparation in the form of the percutaneous preparation, a patch-type estradiol preparation which comprises ethanol as an aid for percutaneous absorption has been already developed and brought substantial results, as described, e.g., in JP-A-57-154122. The term "JP-A" as used herein means an "unexamined published Japanese patent application". Further, a percutaneous preparation containing estradiol which can release a definite amount of estradiol for a prolonged period of time while scarcely causing skin irritation is proposed, as described, e.g., in JP-A-2-102655.
In the aforesaid patch-type preparation containing ethanol, however, it is required to retain a large amount of a water-ethanol mixture, which makes the preparation thick. As a result, it gives a feeling of physical disorder when applied to the skin. It is sometimes observed, furthermore, that an adhesive employed for fixing the preparation onto the skin is plasticized by the ethanol and thus stains the surface of the skin.
In the case of the latter preparation described above, on the other hand, the solubility of estradiol is elevated by using an adhesive comprising a specific copolymer as the main component to thereby increase the estradiol content. Although it shows a satisfactory sustained release, therefore, it cannot be regarded as an excellent preparation from the viewpoint of the releasing dose.
Namely, because estrogen has a poor solubility in common adhesives, when a therapeutically effective amount of estrogen is added to an adhesive, the estrogen would crystallize out from the adhesive. Then, the crystals grow and thus the concentration of the dissolved estrogen is lowered, which seriously lowered the amount of the estrogen to be percutaneously absorbed. When an adhesive, in which estrogen shows a high solubility, is employed, the solubility can be elevated. In this case, however, there is a possibility that the estrogen is released only in an insufficient amount per unit time.